keyword
https://read.qxmd.com/read/37873212/the-role-of-ryanodine-receptor-2-in-drug-associated-learning
#1
Kara R Barber, Velia S Vizcarra, Ashlyn Zilch, Lisa Majuta, Cody C Diezel, Oliver P Culver, Brandon W Hughes, Makoto Taniguchi, John M Streicher, Todd W Vanderah, Arthur C Riegel
Type-2 ryanodine receptor (RyR2) ion channels facilitate the release of Ca 2+ from stores and serve an important function in neuroplasticity. The role for RyR2 in hippocampal-dependent learning and memory is well established and chronic hyperphosphorylation of RyR2 (RyR2P) is associated with pathological calcium leakage and cognitive disorders, including Alzheimer's disease. By comparison, little is known about the role of RyR2 in the ventral medial prefrontal cortex (vmPFC) circuitry important for working memory, decision making, and reward seeking...
October 5, 2023: bioRxiv
https://read.qxmd.com/read/36866681/novel-calmodulin-variant-p-e46k-associated-with-severe-catecholaminergic-polymorphic-ventricular-tachycardia-produces-robust-arrhythmogenicity-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#2
JOURNAL ARTICLE
Jingshan Gao, Takeru Makiyama, Yuta Yamamoto, Takuya Kobayashi, Hisaaki Aoki, Thomas L Maurissen, Yimin Wuriyanghai, Asami Kashiwa, Tomohiko Imamura, Takanori Aizawa, Hai Huang, Hirohiko Kohjitani, Misato Nishikawa, Kazuhisa Chonabayashi, Megumi Fukuyama, Hiromi Manabe, Kouichi Nakau, Tsutomu Wada, Koichi Kato, Futoshi Toyoda, Yoshinori Yoshida, Naomasa Makita, Knut Woltjen, Seiko Ohno, Nagomi Kurebayashi, Takashi Murayama, Takashi Sakurai, Minoru Horie, Takeshi Kimura
BACKGROUND: CaM (calmodulin) is a ubiquitously expressed, multifunctional Ca2+ sensor protein that regulates numerous proteins. Recently, CaM missense variants have been identified in patients with malignant inherited arrhythmias, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the exact mechanism of CaM-related CPVT in human cardiomyocytes remains unclear. In this study, we sought to investigate the arrhythmogenic mechanism of CPVT caused by a novel variant using human induced pluripotent stem cell (iPSC) models and biochemical assays...
March 2023: Circulation. Arrhythmia and Electrophysiology
https://read.qxmd.com/read/35723815/ginsenoside-rg-1-reduces-cardiotoxicity-while-increases-cardiotonic-effect-of-aconitine-in-vitro
#3
JOURNAL ARTICLE
Xin Xu, Xiao-Fang Xie, Yan-Hong Dong, Hui-Qiong Zhang, Cheng Peng
OBJECTIVE: To explore the synergic mechanism of ginsenoside Rg1 (Rg1 ) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs. METHODS: The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg1 for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg1 for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na+ ], potassium ions [K+ ] and calcium ions [Ca2+ ] levels, and Nav1...
August 2022: Chinese Journal of Integrative Medicine
https://read.qxmd.com/read/35703484/hypoxia-induced-sarcoplasmic-reticulum-ca2-leak-is-reversed-by-ryanodine-receptor-stabilizer-jtv-519-in-hl-1-cardiomyocytes
#4
JOURNAL ARTICLE
Minh Duc Trinh, Ivana Fiserova, Lukas Vacek, Marek Marek, Jan Pala, Petr Tousek, Jan Polak
BACKGROUND: To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum. METHODS: The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expres- sion of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment...
June 2022: Anatolian Journal of Cardiology
https://read.qxmd.com/read/32920522/autonomous-activation-of-camkii-exacerbates-diastolic-calcium-leak-during-beta-adrenergic-stimulation-in-cardiomyocytes-of-metabolic-syndrome-rats
#5
JOURNAL ARTICLE
Tatiana Romero-García, Huguet V Landa-Galvan, Natalia Pavón, Martha Mercado-Morales, Héctor H Valdivia, Angélica Rueda
Autonomous Ca2+ /calmodulin-dependent protein kinase II (CaMKII) activation induces abnormal diastolic Ca2+ leak, which leads to triggered arrhythmias in a wide range of cardiovascular diseases, including diabetic cardiomyopathy. In hyperglycemia, Ca2+ handling alterations can be aggravated under stress conditions via the β-adrenergic signaling pathway, which also involves CaMKII activation. However, little is known about intracellular Ca2+ handling disturbances under β-adrenergic stimulation in cardiomyocytes of the prediabetic metabolic syndrome (MetS) model with obesity, and the participation of CaMKII in these alterations...
August 12, 2020: Cell Calcium
https://read.qxmd.com/read/32064746/cardiac-calcium-dysregulation-in-mice-with-chronic-kidney-disease
#6
JOURNAL ARTICLE
Hung-Yen Ke, Li-Han Chin, Chien-Sung Tsai, Feng-Zhi Lin, Yen-Hui Chen, Yung-Lung Chang, Shih-Ming Huang, Yao-Chang Chen, Chih-Yuan Lin
Cardiovascular complications are leading causes of morbidity and mortality in patients with chronic kidney disease (CKD). CKD significantly affects cardiac calcium (Ca2+ ) regulation, but the underlying mechanisms are not clear. The present study investigated the modulation of Ca2+ homeostasis in CKD mice. Echocardiography revealed impaired fractional shortening (FS) and stroke volume (SV) in CKD mice. Electrocardiography showed that CKD mice exhibited longer QT interval, corrected QT (QTc) prolongation, faster spontaneous activities, shorter action potential duration (APD) and increased ventricle arrhythmogenesis, and ranolazine (10 µmol/L) blocked these effects...
February 16, 2020: Journal of Cellular and Molecular Medicine
https://read.qxmd.com/read/31793297/ginsenoside-rb1-improved-diabetic-cardiomyopathy-through-regulating-calcium-signaling-by-alleviating-protein-o-glcnacylation
#7
JOURNAL ARTICLE
Linhui Qin, Jianping Wang, RongRong Zhao, Xiao Zhang, Yingwu Mei
Ginsenoside-Rb1 (Rb1), a major active component of ginseng, has many benefits for cardiovascular disease and diabetes mellitus (DM), but the effect and mechanism on diabetic cardiomyopathy are not clear. In the present study, we found that Rb1-feeding significantly improved cardiac dysfunction and abnormal cardiomyocytes calcium signaling caused by diabetes. This improved calcium signaling was because Rb1 reduced Ca2+ leakage caused by overactivated ryanodine receptor 2 (RyR2) and increased Ca2+ uptake by sarcoplasmic reticulum Ca2+ -ATPase 2a (SERCA 2a)...
December 26, 2019: Journal of Agricultural and Food Chemistry
https://read.qxmd.com/read/31626909/stachydrine-hydrochloride-alleviates-pressure-overload-induced-heart-failure-and-calcium-mishandling-on-mice
#8
COMPARATIVE STUDY
Hui-Hua Chen, Si-Ning Wang, Tong-Tong Cao, Jia-Li Zheng, Jing Tian, Xiao-Li Shan, Pei Zhao, Wei Guo, Ming Xu, Chen Zhang, Rong Lu
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far. AIM OF THE STUDY: The aim of this study was to investigate the protective role of stachydrine hydrochloride in heart failure and elucidate its possible mechanisms of action...
February 10, 2020: Journal of Ethnopharmacology
https://read.qxmd.com/read/31299492/structural-development-of-a-type-1-ryanodine-receptor-ryr1-ca-2-release-channel-inhibitor-guided-by-endoplasmic-reticulum-ca-2-assay
#9
JOURNAL ARTICLE
Shuichi Mori, Hiroto Iinuma, Noriaki Manaka, Mari Ishigami-Yuasa, Takashi Murayama, Yoshiaki Nishijima, Akiko Sakurai, Ryota Arai, Nagomi Kurebayashi, Takashi Sakurai, Hiroyuki Kagechika
Type-1 ryanodine receptor (RyR1) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyR1 are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyR1 causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyR1 channel inhibitor...
October 1, 2019: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/30885011/targeting-ryr2-with-a-phosphorylation-site-specific-nanobody-reverses-dysfunction-of-failing-cardiomyocytes-in-rats
#10
JOURNAL ARTICLE
Tian Li, Yafeng Shen, Fangxing Lin, Wenyan Fu, Shuowu Liu, Chuqi Wang, Jizhou Liang, Xiaoyan Fan, Xuting Ye, Ying Tang, Min Ding, Yongji Yang, Changhai Lei, Shi Hu
Chronic PKA phosphorylation of ryanodine receptor 2 (RyR2) has been shown to increase diastolic sarcoplasmic reticulum (SR) Ca2+ leakage and lead to cardiac dysfunction. We hypothesize that intracellular gene delivery of an RyR2-targeting phosphorylation site-specific nanobody could preserve the contractility of the failing myocardium. In the present study, we acquired RyR2-specific nanobodies from a phage display library that were variable domains of Camelidae heavy chain-only antibodies. One of the nanobodies, AR185, inhibited RyR2 phosphorylation in vitro and was chosen for further investigation...
June 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/28795720/restoring-calcium-homeostasis-in-diabetic-cardiomyocytes-an-investigation-through-mathematical-modelling
#11
JOURNAL ARTICLE
Phonindra Nath Das, Ajay Kumar, Nandadulal Bairagi, Samrat Chatterjee
Calcium homeostasis is a key factor in the regulation of cardiac excitation-contraction coupling. Calcium dynamics in cardiomyocytes is governed by ATP which depends on insulin dependent glucose concentration, via the glucose transporter type 4 (GLUT4) transporter. It would therefore be interesting to see how calcium dynamics changes in a cardiomyocyte under diabetic conditions. We proposed and analysed a four dimensional ordinary differential equation (ODE) model to capture the interdependency of calcium dynamics on glucose uptake and ATP generation...
September 26, 2017: Molecular BioSystems
https://read.qxmd.com/read/28476886/amyloid-%C3%AE-production-is-regulated-by-%C3%AE-2-adrenergic-signaling-mediated-post-translational-modifications-of-the-ryanodine-receptor
#12
JOURNAL ARTICLE
Renaud Bussiere, Alain Lacampagne, Steven Reiken, Xiaoping Liu, Valerie Scheuerman, Ran Zalk, Cécile Martin, Frederic Checler, Andrew R Marks, Mounia Chami
Alteration of ryanodine receptor (RyR)-mediated calcium (Ca2+ ) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca2+ release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe)...
June 16, 2017: Journal of Biological Chemistry
https://read.qxmd.com/read/26005840/s100a1-dna-based-inotropic-therapy-protects-against-proarrhythmogenic-ryanodine-receptor-2-dysfunction
#13
JOURNAL ARTICLE
Julia Ritterhoff, Mirko Völkers, Andreas Seitz, Kristin Spaich, Erhe Gao, Karsten Peppel, Sven T Pleger, Wolfram H Zimmermann, Oliver Friedrich, Rainer H A Fink, Walter J Koch, Hugo A Katus, Patrick Most
Restoring expression levels of the EF-hand calcium (Ca(2+)) sensor protein S100A1 has emerged as a key factor in reconstituting normal Ca(2+) handling in failing myocardium. Improved sarcoplasmic reticulum (SR) function with enhanced Ca(2+) resequestration appears critical for S100A1's cyclic adenosine monophosphate-independent inotropic effects but raises concerns about potential diastolic SR Ca(2+) leakage that might trigger fatal arrhythmias. This study shows for the first time a diminished interaction between S100A1 and ryanodine receptors (RyR2s) in experimental HF...
August 2015: Molecular Therapy
https://read.qxmd.com/read/25348166/genetic-deletion-of-rnd3-rhoe-results-in-mouse-heart-calcium-leakage-through-upregulation-of-protein-kinase-a-signaling
#14
JOURNAL ARTICLE
Xiangsheng Yang, Tiannan Wang, Xi Lin, Xiaojing Yue, Qiongling Wang, Guoliang Wang, Qin Fu, Xun Ai, David Y Chiang, Christina Y Miyake, Xander H T Wehrens, Jiang Chang
RATIONALE: Rnd3, a small Rho GTPase, is involved in the regulation of cell actin cytoskeleton dynamics, cell migration, and proliferation. The biological function of Rnd3 in the heart remains unexplored. OBJECTIVE: To define the functional role of the Rnd3 gene in the animal heart and investigate the associated molecular mechanism. METHODS AND RESULTS: By loss-of-function approaches, we discovered that Rnd3 is involved in calcium regulation in cardiomyocytes...
January 2, 2015: Circulation Research
https://read.qxmd.com/read/25193470/reduced-junctional-na-ca2-exchanger-activity-contributes-to-sarcoplasmic-reticulum-ca2-leak-in-junctophilin-2-deficient-mice
#15
JOURNAL ARTICLE
Wei Wang, Andrew P Landstrom, Qiongling Wang, Michelle L Munro, David Beavers, Michael J Ackerman, Christian Soeller, Xander H T Wehrens
Expression silencing of junctophilin-2 (JPH2) in mouse heart leads to ryanodine receptor type 2 (RyR2)-mediated sarcoplasmic reticulum (SR) Ca(2+) leak and rapid development of heart failure. The mechanism and physiological significance of JPH2 in regulating RyR2-mediated SR Ca(2+) leak remains elusive. We sought to elucidate the role of JPH2 in regulating RyR2-mediated SR Ca(2+) release in the setting of cardiac failure. Cardiac myocytes isolated from tamoxifen-inducible conditional knockdown mice of JPH2 (MCM-shJPH2) were subjected to confocal Ca(2+) imaging...
November 1, 2014: American Journal of Physiology. Heart and Circulatory Physiology
https://read.qxmd.com/read/24068185/ionizing-radiation-regulates-cardiac-ca-handling-via-increased-ros-and-activated-camkii
#16
JOURNAL ARTICLE
Can M Sag, Hendrik A Wolff, Kay Neumann, Marie-Kristin Opiela, Juqian Zhang, Felicia Steuer, Thomas Sowa, Shamindra Gupta, Markus Schirmer, Mark Hünlich, Margret Rave-Fränk, Clemens F Hess, Mark E Anderson, Ajay M Shah, Hans Christiansen, Lars S Maier
Ionizing radiation (IR) is an integral part of modern multimodal anti-cancer therapies. IR involves the formation of reactive oxygen species (ROS) in targeted tissues. This is associated with subsequent cardiac dysfunction when applied during chest radiotherapy. We hypothesized that IR (i.e., ROS)-dependently impaired cardiac myocytes' Ca handling might contribute to IR-dependent cardiocellular dysfunction. Isolated ventricular mouse myocytes and the mediastinal area of anaesthetized mice (that included the heart) were exposed to graded doses of irradiation (sham 4 and 20 Gy) and investigated acutely (after ~1 h) as well as chronically (after ~1 week)...
November 2013: Basic Research in Cardiology
https://read.qxmd.com/read/22962621/cell-model-of-catecholaminergic-polymorphic-ventricular-tachycardia-reveals-early-and-delayed-afterdepolarizations
#17
JOURNAL ARTICLE
Kirsi Kujala, Jere Paavola, Anna Lahti, Kim Larsson, Mari Pekkanen-Mattila, Matti Viitasalo, Annukka M Lahtinen, Lauri Toivonen, Kimmo Kontula, Heikki Swan, Mika Laine, Olli Silvennoinen, Katriina Aalto-Setälä
BACKGROUND: Induced pluripotent stem cells (iPSC) provide means to study the pathophysiology of genetic disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant inherited ion channel disorder predominantly caused by mutations in the cardiac ryanodine receptor (RyR2). In this study the cellular characteristics of CPVT are investigated and whether the electrophysiological features of this mutation can be mimicked using iPSC -derived cardiomyocytes (CM). METHODOLOGY/PRINCIPAL FINDINGS: Spontaneously beating CMs were differentiated from iPSCs derived from a CPVT patient carrying a P2328S mutation in RyR2 and from two healthy controls...
2012: PloS One
https://read.qxmd.com/read/21872879/mechanism-underlying-catecholaminergic-polymorphic-ventricular-tachycardia-and-approaches-to-therapy
#18
JOURNAL ARTICLE
Hiroshi Watanabe, Björn C Knollmann
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by VT induced by adrenergic stress in the absence of structural heart disease and high incidence of sudden cardiac death. The diagnosis is made based on reproducible ventricular tachyarrhythmias including bidirectional VT and polymorphic VT during exercise testings. Two causative genes of CPVT have been identified: RYR2, encoding the cardiac ryanodine receptor (RyR2) Ca(2+) release channel, and CASQ2, encoding cardiac calsequestrin...
November 2011: Journal of Electrocardiology
https://read.qxmd.com/read/21646727/possible-targets-of-therapy-for-catecholaminergic-polymorphic-ventricular-tachycardia-insight-from-a-theoretical-model
#19
JOURNAL ARTICLE
Yi-Hsin Chan, Lung-Sheng Wu, Yung-Hsin Yeh, Chia-Tung Wu, Chun-Li Wang, Nazar Luqman, Wei-Jan Chen, Tzu-Shiu Hsu, Chi-Tai Kuo
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a serious disease with a high mortality but its management is limited. The aim of this study was to investigate specific target sites for therapy in order to find potential management strategies for CPVT. METHODS AND RESULTS: The mutant Ryanodine receptor 2 (RyR2) with reduced stored-overloaded-induced Ca²⁺ release (SOICR) threshold was incorporated into the Luo-Rudy dynamic (LRd) cell model to elucidate the underlying pathologies of CPVT...
2011: Circulation Journal: Official Journal of the Japanese Circulation Society
https://read.qxmd.com/read/20157050/a-leakage-leads-to-failure-roles-of-sarcoplasmic-reticulum-ca2-leak-via-ryr2-in-heart-failure-progression
#20
EDITORIAL
Dayue Darrel Duan
No abstract text is available yet for this article.
April 2010: Hypertension
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